An evaluation of the effect of bortezomib on radiation-induced urinary bladder dysfunction

Sarsarshahi, Sina; Madjd, Zahra; Bozsaky, Eva; Kowaliuk, Jakob; Kueß, Peter; Ghahremani, Mohammad Hossein; Doerr, W.

doi:10.1007/s00066-019-01497-8

Cited by 2 publications

(2 citation statements)

References 29 publications

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“…2,3,30 Systemic therapy approaches, such as the administration of TCDO/WF10, take advantage of immunomodulatory properties. 31,32 Most systemic and local treatments that showed therapeutic modifications did not affect the development of chronic radiation fibrosis. Hyperbaric oxygen treatment is proposed to reduce tissue fibrosis; several clinical studies have revealed beneficial results, but long-term follow-up elucidated the recurrence of fibrosis and poor clinical response of patients.…”

Section: Discussionmentioning

confidence: 99%

Translational Aspects of Nuclear Factor-Kappa B and Its Modulation by Thalidomide on Early and Late Radiation Sequelae in Urinary Bladder Dysfunction

Kowaliuk

Sarsarshahi

Hlawatsch

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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This preclinical study aimed to investigate the role of nuclear factor (NF)-kB in early and late radiogenic sequelae of urinary bladder dysfunction in mice. Thalidomide was applied either during the early or late response phase to determine potential effects of NF-kB inhibition on functional bladder impairment. Methods and Materials: After pelvic irradiation on day 0, female C3H/Neu mice were observed over a period of 360 days and radiation response was evaluated for alterations in bladder functionality and NF-kB activation. Functionality was determined in graded dose experiments (14-24 Gy) and assessed by micturition frequency analysis and transurethral cystotonometry to reveal alterations in voiding and volume. The induction of the NF-kB proteins p50 and p65 was evaluated by immunohistochemistry in response to a single dose of 23 Gy (ED 90). Thalidomide (100 mg/kg/d) was applied intraperitoneally in 3 treatment groups: daily from day 1 to 15, daily from day 16 to 30, and in 2-day-intervals from day 150 to 180. Results: Immunohistochemical analysis showed a biphasic activation of p50 and p65 during the early radiation cystitis phase (day 1-30). After a transient decrease, p50, but not p65, was reactivated permanently leading to increased levels, which suggests an occurrence of chronic inflammation correlated with functional impairment. Both early thalidomide treatments reduced NF-kB activation and shifted the ED 50 value for early radiation cystitis and late radiation sequelae to higher doses. Conclusions: These data clearly demonstrate the involvement of NF-kB signaling in the pathogenesis of radiation-induced urinary bladder dysfunction. Additionally, this study emphasizes that biological targeting of early radiogenic processes has enormous effect on chronic symptoms. The late administration of thalidomide showed no significant effect on functionality.

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Section: Discussionmentioning

confidence: 99%

Translational Aspects of Nuclear Factor-Kappa B and Its Modulation by Thalidomide on Early and Late Radiation Sequelae in Urinary Bladder Dysfunction

Kowaliuk

Sarsarshahi

Hlawatsch

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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“…To date, many compounds have promised improvements in preclinical radioprotection research, most belonging to the third treatment category of RAs. For instance, Bortezomib, a potent proteasome inhibitor currently used in clinics for multiple myeloma treatment, is implicated also in the blockade of NF-κB (104-108) and therefore it was recently investigated in a radiation induced urinary bladder dysfunction mouse model (76). The study employs a daily subcutaneous dose of 0.02 mg/ml of Bortezomib given between days 0-15 or 15-30, at the two acute radiation-induced bladder inflammatory waves, after a single graded radiation dose.…”

Section: Radioprotective Agentsmentioning

confidence: 99%

Pre-clinical Research on Bladder Toxicity After Radiotherapy for Pelvic Cancers: State-of-the Art and Challenges

et al. 2020

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An evaluation of the effect of bortezomib on radiation-induced urinary bladder dysfunction

Cited by 2 publications

References 29 publications

Translational Aspects of Nuclear Factor-Kappa B and Its Modulation by Thalidomide on Early and Late Radiation Sequelae in Urinary Bladder Dysfunction

Translational Aspects of Nuclear Factor-Kappa B and Its Modulation by Thalidomide on Early and Late Radiation Sequelae in Urinary Bladder Dysfunction

Pre-clinical Research on Bladder Toxicity After Radiotherapy for Pelvic Cancers: State-of-the Art and Challenges

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